Citrullinemia

ASA and citrullinemia are two different inherited (genetic) conditions that both cause too much ammonia to build up in the body. 

Ammonia is a waste product normally made when protein is broken don. If the body is unable to remove ammonia, it builds up and can cause serious health problems. 

Babies with the diseases ASA and citrullinemia are identified through newborn screening due to elevated levels of the marker citrullin. 

Because babies always screen positive for both citrullinemia and ASA lyase deficiency, this page contains information about both of these diseases together. 

ASA is a rare, inherited (genetic) disease. Babies with ASA are missing an enzyme called “argininosuccinic acid lyase” that removes ammonia from the blood, which causes the accumulation of ammonia and other harmful substances in the blood. 

Citrullinemia is a rare, inherited (genetic) disease. Babies with citrullinemia are missing an enzyme called "argininosuccinate synthetase" and cannot break down citrulline, which causes the accumulation of ammonia and other harmful substances in the blood. 

Without treatment:

• Ammonia and other harmful substances build up in the baby’s body and can cause life-threatening episodes called metabolic crises, brain damage, and even death. 
• ASA and citrullinemia can also cause problems with liver function, growth, and learning. 

If diagnosed early, treatment can help to prevent these problems and allow children with these diseases to lead the healthiest lives possible. 

• In Ontario, a heel-prick is used to take a few drops of blood from each baby shortly after birth. The blood is tested for more than 25 treatable diseases, including citrullinemia and ASA lyase deficiency. 
• A screen positive result means that more tests are needed to know whether or not a baby has one of these diseases. It does not mean that a baby has a disease. Babies identified at a young age through screening can be treated early to help prevent health problems. 

• • It is normal for parents and guardians to feel worried when their baby has a screen positive result. A ‘screen positive’ result does not mean that a baby has a disease. It means that there is a chance that the baby may have a disease. 
  • Follow-up testing is important to find out whether the baby truly has the disease. 
  • The baby’s health care provider or a health care provider at a newborn screening regional treatment centre will discuss the results with the baby’s family. 
  • Follow-up testing is arranged as soon as possible and involves blood and urine tests. 
  • It can take a few days to weeks to find out if a baby truly has a disease. This waiting period can be hard for families. 

• Normal – The baby does not have ASA or citrullinemia. 
• Abnormal – The baby does have ASA or citrullinemia and will need treatment. The family will be supported by a team of caring specialists at a newborn screening regional treatment centre. 
• Inconclusive – More testing is required. The baby will be followed closely by a specialist to ensure that he/she receives optimal care. 

Most babies with ASA or citrullinemia appear normal at birth but are at risk of high levels of ammonia building up in their body. Some babies get sick very early in life and may be at risk for a serious health condition called a metabolic crisis. 

A metabolic crisis is a life-threatening episode caused by low blood sugar and/or the build-up of harmful substances in the blood. 

Symptoms of a metabolic crisis include: 

• poor feeding 
• vomiting 
• extreme fatigue 
• excessive sleepiness irritability 
• muscle spasms 

If a metabolic crisis is not treated, breathing problems, seizures, coma, brain damage and sometimes death can occur. Screening and treatment aim to prevent metabolic crises and help children with ASA lyase deficiency live healthier lives. 

Early treatment helps to prevent or reduce serious and life-threatening health problems such as: 

• learning delays 
• speech delays 
• co-ordination problems 
• enlarged liver 
• metabolic crisis 
• seizures 

• Treatment for infants with ASA and citrullinemia is started as early as possible and is usually life long. 

  Treatment may include: 

  • a low protein diet and special medical foods or formula 
  • vitamins and supplements prescribed by a metabolic doctor 
  • medication that can help the body get rid of ammonia 
  • liver transplantation 

  Babies with ASA or citrullinemia are cared for by a team, including a metabolic doctor and a dietician, and have their health and development checked regularly. Regular follow-up tests are used to monitor and adjust treatments. If signs of a metabolic crisis are present, urgent medical care is very important. 

• For many children with ASA or citrullinemia, treatment allows them to lead healthy lives with normal growth and intelligence.